Aerosols are increasingly being used for delivering medication for therapeutic treatment of the lungs. For example, in the treatment of asthma, inhalers are commonly used for delivering bronchodilators such as .beta..sub.2 agonists and anti-inflammatory agents such as corticosteroids. Two types of inhalers are in common use, metered dose inhalers (MDIs) and dry powder inhalers (DPIs). Both types have as their object the delivery of medication, which is typically in the form of a solid particulate or powder, into the airways of the lungs at the location of the condition being treated.
In the MDI device, the medication is provided by the pharmaceutical manufacturer in a pressurized aerosol canister, with the medication being suspended or dissolved in a liquid propellant such as a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA). The canister includes a metering valve having a hollow discharge stem which can be depressed inward into the canister to discharge a metered volume of propellant-medication mixture in the form of an aerosol comprising fine droplets of propellant in which particles of the medication are suspended or dissolved. A typical MDI for use with such a canister includes a housing having an actuator and nozzle. The canister is inserted into the housing with the hollow discharge stem of the canister being received in a bore in the actuator. Depressing the closed end of the canister causes the stem to be pushed inward into the canister so that a metered volume of medication is discharged through the nozzle. The housing further defines a flowpath in fluid communication with the nozzle, the flowpath having an outlet at a mouthpiece portion of the housing, such that the aerosolized medication may be inhaled after it exits the mouthpiece portion. The patient either inserts the mouthpiece into the mouth with the lips closed around the mouthpiece, or holds the mouthpiece at a slight distance away from an open mouth. The patient then depresses the canister to discharge the medication, and simultaneously inhales.
Existing MDIs suffer from a number of significant disadvantages. One problem with existing MDIs is poor delivery efficiency of the medication. It has been estimated that on average, with existing MDIs, only about 10 percent of the medication dose which is dispensed from the canister actually reaches the lungs where it can achieve the intended result.
Poor delivery efficiency is caused by a number of factors. One of these is incomplete evaporation of propellant, resulting in a large portion of the metered dose being delivered in a form which cannot be inhaled into the lungs. For effective delivery of aerosolized medication to the airways of the lungs, it is desirable that most of the particles which are inspired be less than about 10 microns (one micron=one-thousandth of a millimeter) in size, and preferably between about 1 micron and 5 microns. Incomplete evaporation of propellant at the outlet of the mouthpiece results in a substantial fraction of the metered dose being delivered in the form of relatively large liquid droplets instead of fine dry particles and/or vapor. Such droplets cannot be inspired, but rather tend to impact the inside of the mouth and at the back of the patient's throat, with the result that much of the medication is swallowed. The local concentration of medication in the mouth and throat can cause local immuno-suppression response, as well as development of fungal infections in the case of corticosteroids. Additionally, swallowing .beta..sub.2 agonists causes relaxation of the smooth muscles of the gastrointestinal tract, which decreases contractility and activity of the stomach. Further, the wasted medication has been estimated to cost U.S. patients about $750 million per year.
Another factor contributing to the problem of poor delivery efficiency is high linear velocity of the aerosol as it exits the mouthpiece, which tends to lead to impaction of the aerosol in the mouth and throat. Ideally, the velocity of the aerosol should match the velocity of the patient's inspired breath so that the particles are entrained in the breath and carried into the lungs. With many existing MDIs, the exit velocity of the aerosol substantially exceeds the velocity of the patient's breath. The high-velocity plume strikes the back of the throat, causing impaction and sticking.
Yet another factor contributing to the poor delivery efficiency of existing MDIs is excessive length of the plume or bolus of aerosol exiting the device. In existing MDIs, this length typically exceeds 25 centimeters, which makes it difficult for the patient to inhale the entire bolus.
In an effort to decrease plume velocity, some MDI designers have added tubular spacers between the aerosol nozzle and the mouthpiece. Although spacers improve delivery efficiency, most of the drug which is discharged from the nozzle impacts and sticks on inner surfaces of the spacer, and is therefore unavailable for inhalation by the user. Thus, MDIs with spacers still suffer from unacceptably low delivery efficiencies.
Furthermore, although dry powder inhalers inherently avoid some of the aforementioned problems of MDIs, such as excessive aerosol velocity, DPIs still suffer from the problem of impaction and sticking of medication on the inner surfaces of the devices, particularly under certain environmental conditions such as high relative humidity, which tends to cause particle aggregation.
Another problem with existing MDIs is the difficulty patients have in coordinating their inhalation with the discharge of the aerosol. In manually operated MDIs, patients frequently inhale too early or too late to effectively inspire the medication. Although a number of breath-actuated MDIs have been devised to address this problem, most of these devices cause discharge at the very onset of the patient's inspiratory effort. Depending on the lung condition being treated and its location, it may often be more desirable for the medication to be discharged near the peak of the patient's inhalation rather than the beginning. Further, it may be desirable to be able to selectively vary the point in the patient's inhalation at which medication is discharged in order to tailor the location of drug delivery to the condition being treated. These advantages are not possible with existing MDIs.
Accordingly, it has been an object of the present invention to provide a method and apparatus for delivering an aerosolized medication in which the respirable fraction of the metered dose (i.e., the fraction in the form of dry particles of the optimum size) is maximized at the exit of the apparatus.
It has been a further object of the present invention to provide a method and apparatus for delivering an aerosolized medication in which the linear velocity of the aerosol at the exit of the apparatus approximately matches the velocity of the patient's inspired breath.
It has been another object of the invention to maximize dispersion and mixing of the drug particles in the bolus of an aerosol within an inhaler apparatus.
It has been a still further object of the present invention to provide a method and apparatus for delivering an aerosolized medication in which the length of the bolus of aerosolized medication which exits the apparatus is as short as possible.
A further object of the invention has been to provide a method and apparatus for maximizing the evaporation of liquid propellant in an inhaler.
Still another object of the invention has been to provide a method and apparatus for delivering an aerosolized medication in which impaction and sticking of medication on the inner walls of the apparatus is minimized.
It has been another object of the present invention to provide a method and apparatus for delivering an aerosolized medication in which the discharge of medication is synchronized with the patient's inspired breath, and in which the timing of the discharge in relation to the patient's breath can be selectively varied.